In collaboration with several Principal Investigators at the CCR/NCI, <em>in silico</em> screening of large small-molecule databases are being conducted for a number of molecular targets relevant for cancer. We are using the <A HREF="http://ccr.cancer.gov/staff/staff.asp?profileid=6282">CADD Group's</a> resources, including our screening <A HREF="http://ccrintra.cancer.gov/cms/annual_reports/projects/printer_friendly_report.asp?ProjID=6190">databases</a> to generate lists of compounds to be purchased from <A HREF= "http://www.chemnavigator.com/nih.asp">commercial suppliers</a>, with the goal of obtaining novel lead compounds in <em>in vitro</em> and/or cell-based assays. <BR> Currently, we are predominantly working on the targets Akt (PH domain), in collaboration with Phillip Dennis, Cancer Therapeutics Branch, CCR, NCI; c-Met, in collaboration with Donald Bottaro, Urologic Oncology Branch, CCR, NCI, and Terrence R. Burke, Jr., Laboratory of Medicinal Chemistry, CCR, NCI; HSP90, in collaboration with Len Neckers, Cell & Cancer Biology Branch, CCR, NCI; polo-Box domain of polo-like kinase 1, in collaboration with Kyung S. Lee, Laboratory of Metabolism, CCR, NCI; Grb2 SH2 domain, in collaboration with Terrence R. Burke, Jr., Laboratory of Medicinal Chemistry, CCR, NCI; PKC, in collaboration with Peter Blumberg, Laboratory of Cancer Biology and Genetics, CCR, NCI, and Victor E. Marquez, Laboratory of Medicinal Chemistry, CCR, NCI; tyrosyl-DNA phosphodiesterase (Tdp1), in collaboration with Yves Pommier, Laboratory of Molecular Pharmacology, CCR, NCI; and imidazoacridone DNA intercalators, in collaboration with Sergei Tarasov, Structural Biophysics Laboratory, CCR, NCI. <BR> Targets for which work has been completed include lecithin retinol acyltransferase (LRAT) and related proteins, in collaboration with Denise Simmons and Luigi DeLuca, formerly Laboratory of Cellular Carcinogenesis and Tumor Promotion, CCR, NCI; and ABCG2, in collaboration with Heidi Bokesch, Molecular Targets Development Program, CCR, NCI. <BR> For Akt, c-Met, and the polo-Box domain of plk1, initial hit sets have been generated, screening samples purchased, and these samples assayed by our collaborators. First results show inhibitory activity for a number of samples in each one of these assay.